Guardians Turned Culprits: NETosis and Its Influence on Pulmonary Fibrosis Development.

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Aleena Varughese, Akarsha Balnadupete, Poornima Ramesh, Thottethodi Subrahmanya Keshava Prasad, Ayshath Burhana Nidha, Yashodhar Bhandary

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Aleena Varughese: Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, India.
Akarsha Balnadupete: Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, India.
Poornima Ramesh: Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, India.
Thottethodi Subrahmanya Keshava Prasad: Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, India.
Ayshath Burhana Nidha: Department of Biochemistry, Mangalore University, Mangalagangothri, Konaje, India.
Yashodhar Bhandary: Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangalore, India. Yash28bhandary@gmail.com. ORCID

PMID: 38717537 DOI: 10.1007/s12033-024-01171-0

Idiopathic pulmonary fibrosis (IPF) is a debilitating, life-threatening irreversible lung disease characterized by the excessive accumulation of fibrotic tissue in the lungs, impairing their function. The exact mechanisms underlying Pulmonary fibrosis (PF) are multifaceted and not yet fully understood. Reports show that during COVID-19 pandemic, PF was dramatically increased due to the hyperactivation of the immune system. Neutrophils and macrophages are the patrolling immune cells that keep the microenvironment balanced. Neutrophil extracellular traps (NETs) are a normal protective mechanism of neutrophils. The chief components of the NETs include DNA, citrullinated histones, and anti-microbial peptides which are released by the activated neutrophils. However, it is becoming increasingly evident that hyperactivation of immune cells can also turn into criminals when it comes to pathological state. Dysregulated NETosis may contribute to sustained inflammation, overactivation of fibroblasts, and ultimately promoting collagen deposition which is the characteristic feature of PF. The role of NETs along with inflammation is attaining greater attention. However, seldom researches are related to the relationship between NETs causing PF. This review highlights the cellular mechanism of NETs-induced pulmonary fibrosis, which could give a better understanding of molecular targets which may be helpful for treating NETs-induced PF.

NADPH NETosis Neutrophil PAD4 Pulmonary fibrosis

Kumar, V. (2020). Pulmonary innate immune response determines the outcome of inflammation during pneumonia and sepsis-associated acute lung injury. Frontiers in Immunology, 11, 1722. https://doi.org/10.3389/fimmu.2020.01722 [DOI: 10.3389/fimmu.2020.01722]
Burn, G. L., Foti, A., Marsman, G., Patel, D. F., & Zychlinsky, A. (2021). The Neutrophil. Immunity, 54(7), 1377��1391. https://doi.org/10.1016/j.immuni.2021.06.006 [DOI: 10.1016/j.immuni.2021.06.006]
Summers, C., Rankin, S. M., Condliffe, A. M., Singh, N., Peters, A. M., & Chilvers, E. R. (2010). Neutrophil kinetics in health and disease. Trends in Immunology, 31(8), 318��324. https://doi.org/10.1016/j.it.2010.05.006 [DOI: 10.1016/j.it.2010.05.006]
Wang, N., He, S., Zheng, Y., & Wang, L. (2023). The value of NLR versus MLR in the short-term prognostic assessment of HBV-related acute-on-chronic liver failure. International Immunopharmacology, 121, 110489. https://doi.org/10.1016/j.intimp.2023.110489 [DOI: 10.1016/j.intimp.2023.110489]
Phatale, V., Famta, P., Srinivasarao, D. A., Vambhurkar, G., Jain, N., Pandey, G., et al. (2023). Neutrophil membrane-based nanotherapeutics: propitious paradigm shift in the management of cancer. Life Sciences. https://doi.org/10.1016/j.lfs.2023.122021 [DOI: 10.1016/j.lfs.2023.122021]
Poto, R., Shamji, M., Marone, G., Durham, S. R., Scadding, G. W., & Varricchi, G. (2022). Neutrophil extracellular traps in asthma: friends or foes? Cells, 11(21), 3521. https://doi.org/10.3390/cells11213521 [DOI: 10.3390/cells11213521]
Desai, J., Mulay, S. R., Nakazawa, D., & Anders, H.-J. (2016). Matters of life and death. How neutrophils die or survive along NET release and is ��NETosis�� = necroptosis? Cellular and molecular life sciences: CMLS, 73(11��12), 2211��2219. https://doi.org/10.1007/s00018-016-2195-0 [DOI: 10.1007/s00018-016-2195-0]
Zawrotniak, M., & Rapala-Kozik, M. (2013). Neutrophil extracellular traps (NETs)��formation and implications. Acta Biochimica Polonica. https://doi.org/10.18388/abp.2013_1983 [DOI: 10.18388/abp.2013_1983]
Leppkes, M., Schick, M., Hohberger, B., Mahajan, A., Knopf, J., Schett, G., et al. (2019). Updates on NET formation in health and disease. Seminars in Arthritis and Rheumatism, 49(3 Supplement), S43��S48. https://doi.org/10.1016/j.semarthrit.2019.09.011 [DOI: 10.1016/j.semarthrit.2019.09.011]
Pietronigro, E. C., Della Bianca, V., Zenaro, E., & Constantin, G. (2017). NETosis in Alzheimer��s Disease. Frontiers in Immunology, 8, 211. https://doi.org/10.3389/fimmu.2017.00211 [DOI: 10.3389/fimmu.2017.00211]
Vogelgesang, A., Grunwald, U., Langner, S., Jack, R., Br��ker, B. M., Kessler, C., & Dressel, A. (2008). Analysis of lymphocyte subsets in patients with stroke and their influence on infection after stroke. Stroke, 39(1), 237��241. https://doi.org/10.1161/STROKEAHA.107.493635 [DOI: 10.1161/STROKEAHA.107.493635]
Henke, M. O., & Ratjen, F. (2007). Mucolytics in cystic fibrosis. Paediatric Respiratory Reviews, 8(1), 24��29. https://doi.org/10.1016/j.prrv.2007.02.009 [DOI: 10.1016/j.prrv.2007.02.009]
Looney, M. R., Nguyen, J. X., Hu, Y., Van Ziffle, J. A., Lowell, C. A., & Matthay, M. A. (2009). Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury. The Journal of Clinical Investigation, 119(11), 3450��3461. https://doi.org/10.1172/JCI38432 [DOI: 10.1172/JCI38432]
Meijer, M., Rijkers, G. T., & van Overveld, F. J. (2013). Neutrophils and emerging targets for treatment in chronic obstructive pulmonary disease. Expert Review of Clinical Immunology, 9(11), 1055��1068. https://doi.org/10.1586/1744666X.2013.851347 [DOI: 10.1586/1744666X.2013.851347]
Fadini, G. P., Menegazzo, L., Rigato, M., Scattolini, V., Poncina, N., Bruttocao, A., et al. (2016). NETosis delays diabetic wound healing in mice and humans. Diabetes, 65(4), 1061��1071. https://doi.org/10.2337/db15-0863 [DOI: 10.2337/db15-0863]
Megens, R. T. A., Vijayan, S., Lievens, D., D��ring, Y., van Zandvoort, M. A. M. J., Grommes, J., et al. (2012). Presence of luminal neutrophil extracellular traps in atherosclerosis. Thrombosis and Haemostasis, 107(3), 597��598. https://doi.org/10.1160/TH11-09-0650 [DOI: 10.1160/TH11-09-0650]
Menegazzo, L., Scattolini, V., Cappellari, R., Bonora, B. M., Albiero, M., Bortolozzi, M., et al. (2018). The antidiabetic drug metformin blunts NETosis in vitro and reduces circulating NETosis biomarkers in vivo. Acta Diabetologica, 55(6), 593��601. https://doi.org/10.1007/s00592-018-1129-8 [DOI: 10.1007/s00592-018-1129-8]
Ponzetto, A., & Figura, N. (2018). Thrombosis of the portal venous system in cirrhotic patients. Annals of Hepatology, 17(6), 1078��1080. https://doi.org/10.5604/01.3001.0012.7209 [DOI: 10.5604/01.3001.0012.7209]
Brazil, J. C., Louis, N. A., & Parkos, C. A. (2013). The role of polymorphonuclear leukocyte trafficking in the perpetuation of inflammation during inflammatory bowel disease. Inflammatory Bowel Diseases, 19(7), 1556��1565. https://doi.org/10.1097/MIB.0b013e318281f54e [DOI: 10.1097/MIB.0b013e318281f54e]
Powe, C. E., Levine, R. J., & Karumanchi, S. A. (2011). Preeclampsia, a disease of the maternal endothelium: the role of antiangiogenic factors and implications for later cardiovascular disease. Circulation, 123(24), 2856��2869. https://doi.org/10.1161/CIRCULATIONAHA.109.853127 [DOI: 10.1161/CIRCULATIONAHA.109.853127]
Arpinati, L., Shaul, M. E., Kaisar-Iluz, N., Mali, S., Mahroum, S., & Fridlender, Z. G. (2020). NETosis in cancer: a critical analysis of the impact of cancer on neutrophil extracellular trap (NET) release in lung cancer patients vs. mice. Cancer Immunology, Immunotherapy, 69(2), 199��213. https://doi.org/10.1007/s00262-019-02474-x [DOI: 10.1007/s00262-019-02474-x]
Pandolfi, L., Bozzini, S., Frangipane, V., Percivalle, E., De Luigi, A., Violatto, M. B., et al. (2021). Neutrophil extracellular traps induce the epithelial-mesenchymal transition: implications in Post-COVID-19 fibrosis. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2021.663303 [DOI: 10.3389/fimmu.2021.663303]
Kolaczkowska, E., & Kubes, P. (2013). Neutrophil recruitment and function in health and inflammation. Nature Reviews. Immunology, 13(3), 159��175. https://doi.org/10.1038/nri3399 [DOI: 10.1038/nri3399]
Nguyen, G. T., Green, E. R., & Mecsas, J. (2017). Neutrophils to the ROScue: mechanisms of NADPH oxidase activation and bacterial resistance. Frontiers in Cellular and Infection Microbiology, 7, 373. https://doi.org/10.3389/fcimb.2017.00373 [DOI: 10.3389/fcimb.2017.00373]
Zeng, M. Y., Miralda, I., Armstrong, C. L., Uriarte, S. M., & Bagaitkar, J. (2019). The roles of NADPH oxidase in modulating neutrophil effector responses. Molecular Oral Microbiology., 34, 27��38. https://doi.org/10.1111/omi.12252 [DOI: 10.1111/omi.12252]
Stafforini, D. M., McIntyre, T. M., Zimmerman, G. A., & Prescott, S. M. (2003). Platelet-activating factor, a pleiotrophic mediator of physiological and pathological processes. Critical Reviews in Clinical Laboratory Sciences, 40(6), 643��672. https://doi.org/10.1080/714037693 [DOI: 10.1080/714037693]
Huang, J., Hong, W., Wan, M., & Zheng, L. (2022). Molecular mechanisms and therapeutic target of NETosis in diseases. MedComm, 3(3), e162. https://doi.org/10.1002/mco2.162 [DOI: 10.1002/mco2.162]
Hann, J., Bueb, J.-L., Tolle, F., & Br��chard, S. (2020). Calcium signaling and regulation of neutrophil functions: still a long way to go. Journal of Leukocyte Biology, 107(2), 285��297. https://doi.org/10.1002/JLB.3RU0719-241R [DOI: 10.1002/JLB.3RU0719-241R]
Chen, Y., Zhang, H., Hu, X., Cai, W., Ni, W., & Zhou, K. (2022). Role of NETosis in central nervous system injury. Oxidative Medicine and Cellular Longevity, 2022, 3235524. https://doi.org/10.1155/2022/3235524 [DOI: 10.1155/2022/3235524]
Angeletti, A., Volpi, S., Bruschi, M., Lugani, F., Vaglio, A., Prunotto, M., et al. (2021). Neutrophil extracellular traps-DNase balance and autoimmunity. Cells, 10(10), 2667. https://doi.org/10.3390/cells10102667 [DOI: 10.3390/cells10102667]
Suzuki, M., Ikari, J., Anazawa, R., Tanaka, N., Katsumata, Y., Shimada, A., et al. (2020). PAD4 deficiency improves bleomycin-induced neutrophil extracellular traps and fibrosis in mouse lung. American Journal of Respiratory Cell and Molecular Biology, 63(6), 806��818. https://doi.org/10.1165/rcmb.2019-0433OC [DOI: 10.1165/rcmb.2019-0433OC]
Guillotin, F., Fortier, M., Portes, M., Demattei, C., Mousty, E., Nouvellon, E., et al. (2023). Vital NETosis vs suicidal NETosis during normal pregnancy and preeclampsia. Frontiers in Cell and Developmental Biology. https://doi.org/10.3389/fcell.2022.1099038 [DOI: 10.3389/fcell.2022.1099038]
Tan, C., Aziz, M., & Wang, P. (2021). The vitals of NETs. Journal of Leukocyte Biology, 110(4), 797��808. https://doi.org/10.1002/JLB.3RU0620-375R [DOI: 10.1002/JLB.3RU0620-375R]
Tian, C., Liu, Y., Li, Z., Zhu, P., & Zhao, M. (2022). Mitochondria related cell death modalities and disease. Frontiers in Cell and Developmental Biology, 10, 832356. https://doi.org/10.3389/fcell.2022.832356 [DOI: 10.3389/fcell.2022.832356]
Potey, P. M., Rossi, A. G., Lucas, C. D., & Dorward, D. A. (2019). Neutrophils in the initiation and resolution of acute pulmonary inflammation: understanding biological function and therapeutic potential. The Journal of Pathology, 247(5), 672��685. https://doi.org/10.1002/path.5221 [DOI: 10.1002/path.5221]
Mazumder, S., Barman, M., Bandyopadhyay, U., & Bindu, S. (2020). Sirtuins as endogenous regulators of lung fibrosis: a current perspective. Life Sciences, 258, 118201. https://doi.org/10.1016/j.lfs.2020.118201 [DOI: 10.1016/j.lfs.2020.118201]
Hayton, C., & Chaudhuri, N. (2017). current treatments in the management of idiopathic pulmonary fibrosis: pirfenidone and nintedanib. Clinical Medicine Insights Therapeutics. https://doi.org/10.1177/1179559X17719126 [DOI: 10.1177/1179559X17719126]
Fathimath Muneesa, M., Shaikh, S. B., Jeena, T. M., & Bhandary, Y. P. (2021). Inflammatory mediators in various molecular pathways involved in the development of pulmonary fibrosis. International Immunopharmacology, 96, 107608. https://doi.org/10.1016/j.intimp.2021.107608 [DOI: 10.1016/j.intimp.2021.107608]
Craig, A., Mai, J., Cai, S., & Jeyaseelan, S. (2009). Neutrophil recruitment to the lungs during bacterial pneumonia. Infection and Immunity, 77(2), 568��575. https://doi.org/10.1128/IAI.00832-08 [DOI: 10.1128/IAI.00832-08]
Porto, B. N., & Stein, R. T. (2016). Neutrophil extracellular traps in pulmonary diseases: too much of a good thing? Frontiers in Immunology, 7, 311. https://doi.org/10.3389/fimmu.2016.00311 [DOI: 10.3389/fimmu.2016.00311]
Andrade, B., Jara-Guti��rrez, C., Paz-Araos, M., V��zquez, M. C., D��az, P., & Murgas, P. (2022). The relationship between reactive oxygen species and the cGAS/STING signaling pathway in the inflammaging process. International Journal of Molecular Sciences, 23(23), 15182. https://doi.org/10.3390/ijms232315182 [DOI: 10.3390/ijms232315182]
Saffarzadeh, M., Juenemann, C., Queisser, M. A., Lochnit, G., Barreto, G., Galuska, S. P., et al. (2012). Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones. PloS One, 7(2), e32366. https://doi.org/10.1371/journal.pone.0032366 [DOI: 10.1371/journal.pone.0032366]
Cheng, O. Z., & Palaniyar, N. (2013). NET balancing: a problem in inflammatory lung diseases. Frontiers in Immunology, 4, 1. https://doi.org/10.3389/fimmu.2013.00001 [DOI: 10.3389/fimmu.2013.00001]
Singhal, A., & Kumar, S. (2022). Neutrophil and remnant clearance in immunity and inflammation. Immunology, 165(1), 22��43. https://doi.org/10.1111/imm.13423 [DOI: 10.1111/imm.13423]
Zhang, S., Jia, X., Zhang, Q., Zhang, L., Yang, J., Hu, C., et al. (2020). Neutrophil extracellular traps activate lung fibroblast to induce polymyositis-related interstitial lung diseases via TLR9-miR-7-Smad2 pathway. Journal of Cellular and Molecular Medicine, 24(2), 1658��1669. https://doi.org/10.1111/jcmm.14858 [DOI: 10.1111/jcmm.14858]
Martins-Cardoso, K., Almeida, V. H., Bagri, K. M., Rossi, M. I. D., Mermelstein, C. S., K��nig, S., & Monteiro, R. Q. (2020). Neutrophil extracellular traps (NETs) promote pro-metastatic phenotype in human breast cancer cells through epithelial-mesenchymal transition. Cancers, 12(6), 1542. https://doi.org/10.3390/cancers12061542 [DOI: 10.3390/cancers12061542]
Stehr, A. M., Wang, G., Demmler, R., Stemmler, M. P., Krug, J., Tripal, P., et al. (2022). Neutrophil extracellular traps drive epithelial-mesenchymal transition of human colon cancer. The Journal of Pathology, 256(4), 455��467. https://doi.org/10.1002/path.5860 [DOI: 10.1002/path.5860]
Arroyo, R., Khan, M. A., Echaide, M., P��rez-Gil, J., & Palaniyar, N. (2019). SP-D attenuates LPS-induced formation of human neutrophil extracellular traps (NETs), protecting pulmonary surfactant inactivation by NETs. Communications Biology, 2(1), 1��13. https://doi.org/10.1038/s42003-019-0662-5 [DOI: 10.1038/s42003-019-0662-5]
Crouch, E., & Wright, J. R. (2001). Surfactant proteins A and D and pulmonary host defense. Annual Review of Physiology, 63(1), 521��554. https://doi.org/10.1146/annurev.physiol.63.1.521 [DOI: 10.1146/annurev.physiol.63.1.521]
Hao, Y., Baker, D., & Ten Dijke, P. (2019). TGF-��-mediated epithelial-mesenchymal transition and cancer metastasis. International Journal of Molecular Sciences, 20(11), 2767. https://doi.org/10.3390/ijms20112767 [DOI: 10.3390/ijms20112767]
Kim, I.-S., Yang, W.-S., & Kim, C.-H. (2023). Physiological properties, functions, and trends in the matrix metalloproteinase inhibitors in inflammation-mediated human diseases. Current Medicinal Chemistry, 30(18), 2075��2112. https://doi.org/10.2174/0929867329666220823112731 [DOI: 10.2174/0929867329666220823112731]
Paez-Ribes, M., Gonz��lez-Gualda, E., Doherty, G. J., & Mu��oz-Esp��n, D. (2019). Targeting senescent cells in translational medicine. EMBO Molecular Medicine, 11(12), 10234. https://doi.org/10.15252/emmm.201810234 [DOI: 10.15252/emmm.201810234]
Plataki, M., Koutsopoulos, A. V., Darivianaki, K., Delides, G., Siafakas, N. M., & Bouros, D. (2005). Expression of apoptotic and antiapoptotic markers in epithelial cells in idiopathic pulmonary fibrosis. Chest, 127(1), 266��274. https://doi.org/10.1378/chest.127.1.266 [DOI: 10.1378/chest.127.1.266]
Uhal, B. D., Joshi, I., Hughes, W. F., Ramos, C., Pardo, A., & Selman, M. (1998). Alveolar epithelial cell death adjacent to underlying myofibroblasts in advanced fibrotic human lung. The American Journal of Physiology. https://doi.org/10.1152/ajplung.1998.275.6.L1192 [DOI: 10.1152/ajplung.1998.275.6.L1192]
Hagimoto, N., Kuwano, K., Nomoto, Y., Kunitake, R., & Hara, N. (1997). Apoptosis and expression of Fas/Fas ligand mRNA in bleomycin-induced pulmonary fibrosis in mice. American Journal of Respiratory Cell and Molecular Biology, 16(1), 91��101. https://doi.org/10.1165/ajrcmb.16.1.8998084 [DOI: 10.1165/ajrcmb.16.1.8998084]
Wang, R., Ibarra-Sunga, O., Verlinski, L., Pick, R., & Uhal, B. D. (2000). Abrogation of bleomycin-induced epithelial apoptosis and lung fibrosis by captopril or by a caspase inhibitor. American Journal of Physiology-Lung Cellular and Molecular Physiology, 279(1), L143��L151. https://doi.org/10.1152/ajplung.2000.279.1.L143 [DOI: 10.1152/ajplung.2000.279.1.L143]
Uhal, B. D. (2008). The role of apoptosis in pulmonary fibrosis. European Respiratory Review, 17(109), 138��144. https://doi.org/10.1183/09059180.00010906 [DOI: 10.1183/09059180.00010906]
Yu, Y., Tang, D., & Kang, R. (2015). Oxidative stress-mediated HMGB1 biology. Frontiers in Physiology. https://doi.org/10.3389/fphys.2015.00093 [DOI: 10.3389/fphys.2015.00093]
Hsieh, Y.-T., Chou, Y.-C., Kuo, P.-Y., Tsai, H.-W., Yen, Y.-T., Shiau, A.-L., & Wang, C.-R. (2022). Down-regulated miR-146a expression with increased neutrophil extracellular traps and apoptosis formation in autoimmune-mediated diffuse alveolar hemorrhage. Journal of Biomedical Science, 29, 62. https://doi.org/10.1186/s12929-022-00849-4 [DOI: 10.1186/s12929-022-00849-4]
Pergolizzi, J. V., LeQuang, J. A., Varrassi, M., Breve, F., Magnusson, P., & Varrassi, G. (2023). What do we need to know about rising rates of idiopathic pulmonary fibrosis? A narrative review and update. Advances in Therapy, 40(4), 1334��1346. https://doi.org/10.1007/s12325-022-02395-9 [DOI: 10.1007/s12325-022-02395-9]
Kaplan, M. J., & Radic, M. (2012). Neutrophil extracellular traps (NETs): double-edged swords of innate immunity. Journal of Immunology, 189(6), 2689��2695. https://doi.org/10.4049/jimmunol.1201719 [DOI: 10.4049/jimmunol.1201719]
Gray, R. D., McCullagh, B. N., & McCray, P. B. (2015). NETs and CF lung disease: current status and future prospects. Antibiotics, 4(1), 62��75. https://doi.org/10.3390/antibiotics4010062 [DOI: 10.3390/antibiotics4010062]
French, J. K., Hurst, N. P., Zalewski, P. D., Valente, L., & Forbes, I. J. (1987). Calcium ionophore A23187 enhances human neutrophil superoxide release, stimulated by phorbol dibutyrate, by converting phorbol ester receptors from a low- to high-affinity state. FEBS Letters, 212(2), 242��246. https://doi.org/10.1016/0014-5793(87)81353-4 [DOI: 10.1016/0014-5793(87)81353-4]
Ferrari, G., Pang, L. Y., De Moliner, F., Vendrell, M., Reardon, R. J. M., Higgins, A. J., et al. (2022). Effective penetration of a liposomal formulation of bleomycin through ex-vivo skin explants from two different species. Cancers, 14(4), 1083. https://doi.org/10.3390/cancers14041083 [DOI: 10.3390/cancers14041083]
Saccone, N., Bass, J., & Ramirez, M. L. (2022). Bleomycin-induced lung injury after intravenous iron administration. Cureus, 14(7), e27531. https://doi.org/10.7759/cureus.27531 [DOI: 10.7759/cureus.27531]
Wang, H., Zhang, Y., Wang, Q., Wei, X., Wang, H., & Gu, K. (2021). The regulatory mechanism of neutrophil extracellular traps in cancer biological behavior. Cell & Bioscience, 11(1), 193. https://doi.org/10.1186/s13578-021-00708-z [DOI: 10.1186/s13578-021-00708-z]
Burger, R. M., Peisach, J., & Horwitz, S. B. (1981). Activated bleomycin. A transient complex of drug, iron, and oxygen that degrades DNA. The Journal of Biological Chemistry, 256(22), 11636��11644. [DOI: 10.1016/S0021-9258(19)68452-8]
Yan, S., Li, M., Liu, B., Ma, Z., & Yang, Q. (2023). Neutrophil extracellular traps and pulmonary fibrosis: an update. Journal of Inflammation, 20(1), 2. https://doi.org/10.1186/s12950-023-00329-y [DOI: 10.1186/s12950-023-00329-y]
Manzoor, S., Mariappan, N., Zafar, I., Wei, C.-C., Ahmad, A., Surolia, R., et al. (2020). Cutaneous lewisite exposure causes acute lung injury. Annals of the New York Academy of Sciences, 1479(1), 210��222. https://doi.org/10.1111/nyas.14346 [DOI: 10.1111/nyas.14346]
Li, C., Srivastava, R. K., Weng, Z., Croutch, C. R., Agarwal, A., Elmets, C. A., et al. (2016). Molecular mechanism underlying pathogenesis of lewisite-induced cutaneous blistering and inflammation. The American Journal of Pathology, 186(10), 2637��2649. https://doi.org/10.1016/j.ajpath.2016.06.012 [DOI: 10.1016/j.ajpath.2016.06.012]
Surolia, R., Li, F. J., Wang, Z., Kashyap, M., Srivastava, R. K., Traylor, A. M., et al. (2021). NETosis in the pathogenesis of acute lung injury following cutaneous chemical burns. JCI Insight, 6(10), e147564. https://doi.org/10.1172/jci.insight.147564 [DOI: 10.1172/jci.insight.147564]
Cui, X., Zhang, Y., Lu, Y., & Xiang, M. (2022). ROS and endoplasmic reticulum stress in pulmonary disease. Frontiers in Pharmacology. https://doi.org/10.3389/fphar.2022.879204 [DOI: 10.3389/fphar.2022.879204]
Wang, P., Liu, D., Zhou, Z., Liu, F., Shen, Y., You, Q., et al. (2023). The role of protein arginine deiminase 4-dependent neutrophil extracellular traps formation in ulcerative colitis. Frontiers in Immunology, 14, 1144976. https://doi.org/10.3389/fimmu.2023.1144976 [DOI: 10.3389/fimmu.2023.1144976]
O��Sullivan, K. M., & Holdsworth, S. R. (2021). Neutrophil extracellular traps: A potential therapeutic target in MPO-ANCA associated vasculitis? Frontiers in Immunology, 12, 635188. https://doi.org/10.3389/fimmu.2021.635188 [DOI: 10.3389/fimmu.2021.635188]
d��Alessandro, M., Conticini, E., Bergantini, L., Cameli, P., Cantarini, L., Frediani, B., & Bargagli, E. (2022). Neutrophil extracellular traps in ANCA-associated vasculitis and interstitial lung disease: a scoping review. Life (Basel, Switzerland), 12(2), 317. https://doi.org/10.3390/life12020317 [DOI: 10.3390/life12020317]
Hornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., Kono, H., Rock, K. L., et al. (2008). Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nature Immunology, 9(8), 847��856. https://doi.org/10.1038/ni.1631 [DOI: 10.1038/ni.1631]
Li, T., Zhang, Z., Li, X., Dong, G., Zhang, M., Xu, Z., & Yang, J. (2020). Neutrophil extracellular traps: signaling properties and disease relevance. Mediators of Inflammation, 2020, 9254087. https://doi.org/10.1155/2020/9254087 [DOI: 10.1155/2020/9254087]
Janiuk, K., Jab��o��ska, E., & Garley, M. (2021). Significance of NETs formation in COVID-19. Cells, 10(1), 151. https://doi.org/10.3390/cells10010151 [DOI: 10.3390/cells10010151]
Peukert, K., Steinhagen, F., Fox, M., Feuerborn, C., Schulz, S., Seeliger, B., et al. (2022). Tetracycline ameliorates silica-induced pulmonary inflammation and fibrosis via inhibition of caspase-1. Respiratory Research, 23(1), 21. https://doi.org/10.1186/s12931-022-01937-7 [DOI: 10.1186/s12931-022-01937-7]
Zou, Y., Chen, X., Xiao, J., Bo Zhou, D., Xiao Lu, X., Li, W., et al. (2018). Neutrophil extracellular traps promote lipopolysaccharide-induced airway inflammation and mucus hypersecretion in mice. Oncotarget, 9(17), 13276��13286. https://doi.org/10.18632/oncotarget.24022 [DOI: 10.18632/oncotarget.24022]
Ciesielska, A., Matyjek, M., & Kwiatkowska, K. (2021). TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling. Cellular and Molecular Life Sciences: CMLS, 78(4), 1233��1261. https://doi.org/10.1007/s00018-020-03656-y [DOI: 10.1007/s00018-020-03656-y]
Tsukamoto, H., Takeuchi, S., Kubota, K., Kobayashi, Y., Kozakai, S., Ukai, I., et al. (2018). Lipopolysaccharide (LPS)-binding protein stimulates CD14-dependent Toll-like receptor 4 internalization and LPS-induced TBK1��IKK��IRF3 axis activation. Journal of Biological Chemistry, 293(26), 10186��10201. https://doi.org/10.1074/jbc.M117.796631 [DOI: 10.1074/jbc.M117.796631]
Krinsky, N., Sizikov, S., Nissim, S., Dror, A., Sas, A., Prinz, H., et al. (2023). NETosis induction reflects COVID-19 severity and long COVID: insights from a 2-center patient cohort study in Israel. Journal of Thrombosis and Haemostasis: JTH, 21(9), 2569��2584. https://doi.org/10.1016/j.jtha.2023.02.033 [DOI: 10.1016/j.jtha.2023.02.033]
Vorobjeva, N. V., & Chernyak, B. V. (2020). NETosis: molecular mechanisms, role in physiology and pathology. Biochemistry Biokhimiia, 85(10), 1178��1190. https://doi.org/10.1134/S0006297920100065 [DOI: 10.1134/S0006297920100065]
Holmes, C. L., Shim, D., Kernien, J., Johnson, C. J., Nett, J. E., & Shelef, M. A. (2019). Insight into neutrophil extracellular traps through systematic evaluation of citrullination and peptidylarginine deiminases. Journal of Immunology Research, 2019, 2160192. https://doi.org/10.1155/2019/2160192 [DOI: 10.1155/2019/2160192]
Jo, A., & Kim, D. W. (2023). Neutrophil extracellular traps in airway diseases: pathological roles and therapeutic implications. International Journal of Molecular Sciences, 24(5), 5034. https://doi.org/10.3390/ijms24055034 [DOI: 10.3390/ijms24055034]
Ciesielski, O., Biesiekierska, M., Panthu, B., Soszy��ski, M., Pirola, L., & Balcerczyk, A. (2022). Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives. Cellular and Molecular Life Sciences: CMLS, 79(2), 94. https://doi.org/10.1007/s00018-022-04126-3 [DOI: 10.1007/s00018-022-04126-3]
Veras, F. P., Gomes, G. F., Silva, B. M. S., Caetit��, D. B., Almeida, C. J. L. R., Silva, C. M. S., et al. (2023). Targeting neutrophils extracellular traps (NETs) reduces multiple organ injury in a COVID-19 mouse model. Respiratory Research, 24, 66. https://doi.org/10.1186/s12931-023-02336-2 [DOI: 10.1186/s12931-023-02336-2]
Sharma, P., Garg, N., Sharma, A., Capalash, N., & Singh, R. (2019). Nucleases of bacterial pathogens as virulence factors, therapeutic targets and diagnostic markers. International Journal of Medical Microbiology: IJMM, 309(8), 151354. https://doi.org/10.1016/j.ijmm.2019.151354 [DOI: 10.1016/j.ijmm.2019.151354]
Lee, Y. Y., Park, H. H., Park, W., Kim, H., Jang, J. G., Hong, K. S., et al. (2021). Long-acting nanoparticulate DNase-1 for effective suppression of SARS-CoV-2-mediated neutrophil activities and cytokine storm. Biomaterials, 267, 120389. https://doi.org/10.1016/j.biomaterials.2020.120389 [DOI: 10.1016/j.biomaterials.2020.120389]
Sallai, K., Nagy, E., Derfalvy, B., M��zes, G., & Gergely, P. (2005). Antinucleosome antibodies and decreased deoxyribonuclease activity in sera of patients with systemic lupus erythematosus. Clinical and Diagnostic Laboratory Immunology, 12(1), 56��59. https://doi.org/10.1128/CDLI.12.1.56-59.2005 [DOI: 10.1128/CDLI.12.1.56-59.2005]
Nishino, T., & Morikawa, K. (2002). Structure and function of nucleases in DNA repair: shape, grip and blade of the DNA scissors. Oncogene, 21(58), 9022��9032. https://doi.org/10.1038/sj.onc.1206135 [DOI: 10.1038/sj.onc.1206135]
Li, Y., Wang, W., Yang, F., Xu, Y., Feng, C., & Zhao, Y. (2019). The regulatory roles of neutrophils in adaptive immunity. Cell Communication and Signaling, 17(1), 147. https://doi.org/10.1186/s12964-019-0471-y [DOI: 10.1186/s12964-019-0471-y]
Wu, H., Daouk, S., Kebbe, J., Chaudry, F., Harper, J., & Brown, B. (2022). Low-dose versus high-dose dexamethasone for hospitalized patients with COVID-19 pneumonia: a randomized clinical trial. PLoS ONE, 17(10), e0275217. https://doi.org/10.1371/journal.pone.0275217 [DOI: 10.1371/journal.pone.0275217]
Chen, T., Li, Y., Sun, R., Hu, H., Liu, Y., Herrmann, M., et al. (2021). Receptor-mediated NETosis on neutrophils. Frontiers in Immunology, 12, 775267. https://doi.org/10.3389/fimmu.2021.775267 [DOI: 10.3389/fimmu.2021.775267]
Ma, Y. (2021). Role of neutrophils in cardiac injury and repair following myocardial infarction. Cells, 10(7), 1676. https://doi.org/10.3390/cells10071676 [DOI: 10.3390/cells10071676]
Kenny, E. F., Herzig, A., Kr��ger, R., Muth, A., Mondal, S., Thompson, P. R., et al. (2017). Diverse stimuli engage different neutrophil extracellular trap pathways. eLife, 6, 24437. https://doi.org/10.7554/eLife.24437 [DOI: 10.7554/eLife.24437]
Hodgman, M. J., & Garrard, A. R. (2012). A review of acetaminophen poisoning. Critical Care Clinics, 28(4), 499��516. https://doi.org/10.1016/j.ccc.2012.07.006 [DOI: 10.1016/j.ccc.2012.07.006]
Dekhuijzen, P. N. R., & van Beurden, W. J. C. (2006). The role for N-acetylcysteine in the management of COPD. International Journal of Chronic Obstructive Pulmonary Disease, 1(2), 99��106. https://doi.org/10.2147/copd.2006.1.2.99 [DOI: 10.2147/copd.2006.1.2.99]
Halasi, M., Wang, M., Chavan, T. S., Gaponenko, V., Hay, N., & Gartel, A. L. (2013). ROS inhibitor N-acetyl-l-cysteine antagonizes the activity of proteasome inhibitors. The Biochemical Journal, 454(2), 201��208. https://doi.org/10.1042/BJ20130282 [DOI: 10.1042/BJ20130282]

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